POS0491 A COMPREHENSIVE PROFILE OF CHEMOKINES IN THE PERIPHERAL BLOOD AND VASCULAR TISSUE OF PATIENTS WITH TAKAYASU ARTERITIS
Authors: X. Kong, S. Wu, X. Dai, W. Yu, J. Wang, Y. Sun, Z. Ji, L. MA, X. Dai, H. Chen, L. MA, L. Jiang
Journal: Annals of the Rheumatic Diseases (2022)

Background Takayasu arteritis (TAK) is a chronic granulomatous large vessel vasculitis with multiple immune cells involved [1]. In TAK, vascular lesions originate from the vascular adventitia. The vascular adventitia is rich in vasa vasorum, which can transport peripheral immune cells to active vascular lesions in the early stage of lesion development [2]. Thus, chemokines played critical roles in the pathogenesis of TAK. It has been reported that the levels of RANTES, CCL2, CCL20, CXCL8, and CXCL10 were elevated in TAK, and their levels were correlated with disease activity [3, 4]. However, the profile of chemokines in TAK has not been clearly elucidated. Objectives This study aimed to investigate chemokine profile in peripheral blood and vascular tissue of patients with TAK. Methods A total of 58 patients with TAK and 53 healthy controls were enrolled. Chemokine array assay was performed in five patients with TAK and three controls. Chemokines with higher levels were preliminarily validated in 20 patients and controls. The validated chemokines were further confirmed in another group of samples with 25 patients and 25 controls. Their expression and distribution were also examined in vascular tissue from 8 patients and 5 controls. Correlations between these chemokines and peripheral immune cells, cytokines, disease activity parameters were analyzed. Their serum changes were also investigated in these 45 patients after glucocorticoids and immunosuppressive treatment. Results Patients and controls were age and sex-matched. Twelve higher chemokines and 4 lower chemokines were found based on the chemokine array. After validation, increase of 5 chemokines were confirmed in patients with TAK, including CCL22, RANTES, CXCL16, CXCL11, and IL-16. Their expressions were also increased in vascular tissue of patients with TAK. In addition, levels of RANTES and IL-16 were positively correlated with peripheral CD3+CD4+ T cell numbers. Close localization of CCL22, CXCL11 or IL-16 with inflammatory cells were also observed in TAK vascular tissue. No correlations were found between these chemokines and cytokines (IL-6, IL-17, IFN-γ) or inflammatory parameters (ESR, CRP). No differences were observed regarding with these chemokines between active and inactive patients. After treatment, increase of CCL22 and decrease of RANTES, CXCL16 were found, while no changes were showed in levels of CXCL11 and IL-16. Conclusion CCL22, RANTES, CXCL16, CXCL11, and IL-16 were identified as the major chemokines involved in the recruitment of immune cells in the vascular tissue of patients with TAK. Additionally, the persistently high levels of CCL22, CXCL11, and IL-16 observed after treatment indicate their role in vascular chronic inflammation or fibrosis and demonstrate the need for developing more efficacious treatment options. References [1]Seyahi E. Takayasu arteritis: an update. Curr Opin Rheumatol. 2017 Jan;29(1):51-56. [2]Corbera-Bellalta M, Planas-Rigol E, Lozano E, Terrades-García N, Alba MA, Prieto-González S, García-Martínez A, Albero R, Enjuanes A, Espígol-Frigolé G, Hernández-Rodríguez J, Roux-Lombard P, Ferlin WG, Dayer JM, Kosco-Vilbois MH, Cid MC. Blocking interferon γ reduces expression of chemokines CXCL9, CXCL10 and CXCL11 and decreases macrophage infiltration in ex vivo cultured arteries from patients with giant cell arteritis. Ann Rheum Dis. 2016 Jun;75(6):1177-86. [3]Noris M, Daina E, Gamba S, Bonazzola S, Remuzzi G. Interleukin-6 and RANTES in Takayasu arteritis: a guide for therapeutic decisions? Circulation. 1999 Jul 6;100(1):55-60. [4]Dong H, Zhang Y, Zou Y, Chen Y, Yue J, Liu H, Jiang X. Elevated chemokines concentration is associated with disease activity in Takayasu arteritis. Cytokine. 2021 Jul;143:155515. Disclosure of Interests None declared.